Identification of EphB6 variant-derived epitope peptides recognized by cytotoxic T-lymphocytes from HLA-A24+ malignant glioma patients.

Abstract

We found previously that EphB6, a member of the erythropoietin-producing hepatocyte (Eph) receptor tyrosine kinase family, was preferentially expressed in malignant gliomas. In the present study, RT-PCR revealed a putative secretory variant form of human EphB6 that was expressed in the majority of glioma cell lines, though not in normal tissues. The variant has a unique 54 amino acid sequence that is not found in the normal EphB6. Therefore, we attempted to determine the antigenic peptides unique to the variant for immunotherapy. The two variant-derived peptides had the ability to bind to HLA-A2402 molecules and each of them could induce cytotoxic T-lymphocytes (CTLs) in vitro in peripheral blood mononuclear cells of HLA-A24(+) glioma patients. Furthermore, the cytotoxicity was mediated by peptide-specific CD8(+) T cells in an HLA-A24 restricted manner. Taken together, the two peptides derived from the variant of EphB6 might be appropriate targets for peptide-based specific immunotherapy to HLA-A24(+) patients with malignant glioma.

• Authors: Mingyue Jin, Yoshihiro Komohara, Shigeki Shichijo, Mamoru Harada, Ryuya Yamanaka, Shigeaki Miyamoto, Junichi Nikawa, Kyogo Itoh, Akira Yamada
• Journal: Oncology reports (Oncol Rep) Vol. 19 Issue 5 Pg. 1277-83 (May 2008) ISSN: 1021-335X [Print] Greece
• PMID: 18425388 (Publication Type: Journal Article)

Chemical References

• DNA, Complementary
• Epitopes
• HLA-A Antigens
• HLA-A24 Antigen
• Peptides
• Receptor, EphB6

Topics

• Amino Acid Sequence
• Brain Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• DNA, Complementary (metabolism)
• Epitopes (chemistry)
• Gene Expression Regulation
• Glioma (metabolism, pathology)
• HLA-A Antigens (chemistry)
• HLA-A24 Antigen
• Humans
• Immunotherapy (methods)
• Molecular Sequence Data
• Peptides (chemistry)
• Receptor, EphB6 (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes, Cytotoxic (chemistry, immunology)